Peptide-targeted liposomal delivery for treatment, diagnosis, and imaging of diseases and disorders

Abstract

The present invention relates in part to compositions for targeted delivery of an agent and agent delivery systems comprising a novel tissue-targeting peptide ligand (CKPFDRALC) (SEQ ID NO: 1) named ART-2. In certain aspects, the ART-2-coated liposomes encapsulating an agent, such as a therapeutic agent, diagnostic agent, imaging agent, or any combination thereof, were more effective in inhibiting, diagnosing, or imaging a disease or disorder, such as an arthritis progression, than control, despite a comparable safety profile.

We claim: 
     
       1. A composition comprising at least one isolated peptide comprising the amino acid sequence CKPFDRALC (SEQ ID NO: 1), wherein the peptide selectively targets inflamed synovial tissue. 
     
     
       2. The composition of  claim 1 , wherein the composition further comprises a liposome, lipid, pharmaceutically acceptable carrier, or any combination thereof. 
     
     
       3. The composition of  claim 1 , wherein the peptide is conjugated to a liposome, lipid, pharmaceutically acceptable carrier, or any combination thereof. 
     
     
       4. The composition of  claim 1 , wherein the composition further comprises an agent selected from the group consisting of a protein, peptide, peptidomimetic, antibody, ribozyme, vector, nucleic acid molecule, antisense nucleic acid, small molecule drug, and any combination thereof. 
     
     
       5. The composition of  claim 1 , wherein the composition further comprises an agent selected from the group consisting of: a therapeutic agent, prophylactic agent, diagnostic agent, imaging agent, contrast agent, microparticle, nanoparticle, and any combination thereof. 
     
     
       6. The composition of  claim 5 , wherein the therapeutic agent is selected from the group consisting of a glucocorticoid, biologic, anti-arthritis drug, and any combination thereof. 
     
     
       7. The composition of  claim 6 , wherein the glucocorticoid is selected from the group consisting of cortisol (hydrocortisone), cortisone, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, fludrocortisone acetate, deoxycorticosterone acetate, and any combination thereof. 
     
     
       8. The composition of  claim 5 , wherein the contrast agent is selected from the group consisting of radiocontrast medium, iodinated contrast agent, iodine, ipodate sodium, diatrizoate, metrizoate, iothalamate, ioxaglate, iopamidol, iohexol, ioxilan, iopromide, iodixanol, ioversol, barium, MRI contrast agent, gadolinium, ultrasound contrast agent, saline solution, and any combination thereof. 
     
     
       9. A method of delivering an agent to a biological tissue, the method comprising administering a composition to a subject in need thereof, wherein the composition comprises the agent and at least one isolated peptide comprising the amino acid sequence CKPFDRALC (SEQ ID NO: 1), and
 wherein the peptide selectively targets inflamed synovial tissue. 
 
     
     
       10. The method of  claim 9 , wherein the peptide is conjugated to a liposome, lipid, pharmaceutically acceptable carrier, or any combination thereof. 
     
     
       11. The method of  claim 9 , wherein the peptide is further conjugated to an agent selected from the group consisting of a therapeutic agent, prophylactic agent, diagnostic agent, imaging agent, contrast agent, microparticle, nanoparticle, and any combination thereof. 
     
     
       12. A method of treating a disease or disorder of a joint in a subject by delivery of an agent to a biological tissue of a subject, the method comprising administering the composition of  claim 2  to a subject in need thereof. 
     
     
       13. The method of  claim 12 , wherein the peptide is conjugated to a liposome, lipid, pharmaceutically acceptable carrier, or any combination thereof. 
     
     
       14. The method of  claim 12 , wherein the peptide is further conjugated to an agent selected from the group consisting of a protein, peptide, peptidomimetic, antibody, ribozyme, vector, nucleic acid molecule, antisense nucleic acid, small molecule drug, and any combination thereof. 
     
     
       15. The method of  claim 12 , wherein the peptide is further conjugated to an agent selected from the group consisting of a therapeutic agent, prophylactic agent, diagnostic agent, imaging agent, contrast agent, microparticle, nanoparticle, and any combination thereof. 
     
     
       16. The method of  claim 15 , wherein the therapeutic agent is selected from the group consisting of a glucocorticoid, biologic, anti-arthritis drug, and any combination thereof. 
     
     
       17. The method of  claim 16 , wherein the glucocorticoid is selected from the group consisting of: cortisol (hydrocortisone), cortisone, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, fludrocortisone acetate, deoxycorticosterone acetate, and any combination thereof. 
     
     
       18. The method of  claim 12 , wherein the disease or disorder is selected from the group consisting of: immune-mediated disease, autoimmune disease, inflammatory disease, autoinflammatory diseases, and any combination thereof. 
     
     
       19. The method of  claim 12 , wherein the disease or disorder is rheumatoid arthritis. 
     
     
       20. A method of diagnosing a disease or disorder of a joint in a subject by delivery of an agent to a biological tissue of a subject, the method comprising administering the composition of  claim 2  to a subject in need thereof. 
     
     
       21. A method of imaging inflamed synovial tissue in a subject by delivery of an agent to a biological tissue of a subject, the method comprising administering the composition of  claim 2  to a subject in need thereof. 
     
     
       22. A composition for targeted delivery of an agent, the composition comprising at least one isolated peptide conjugated to a liposome, lipid, pharmaceutically acceptable carrier, or any combination thereof,
 wherein the peptide is a tissue-targeting peptide comprising the amino acid sequence CKPFDRALC (SEQ ID NO: 1).